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Biomarkers in neonatal hypoxic-ischemic encephalopathy-Review of the literature to date and future directions for research.
Handb Clin Neurol. 2019;162:281-293
Authors: Murray DM
Abstract
The widespread introduction of therapeutic hypothermia as a standard of care in hypoxic-ischemic encephalopathy (HIE) has brought increasing pressure on clinicians to make an early and accurate assessment of the degree of hypoxic injury (HI) that has occurred and the severity of the encephalopathy that will ensue. No single blood-based marker is currently robust enough to detect significant HI or predict outcome. However, research in the field has been active in the last 10 years and we know that HIE is associated with predictable alterations in the expression of a number of inflammatory proteins, neuron-specific proteins, metabolite pathways, and microRNA. These alterations evolve quickly over the first hours and days of life. Predictive power varies depending on the timing of measurement of the biomarker, the sample type, and the case mix of the cohort examined. Combining clinical data with biochemical measurements is currently the most likely path toward improved detection and prediction of outcome in neonatal HIE.
PMID: 31324315 [PubMed - in process]

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A highly sensitive ultra-high performance liquid chromatography/tandem mass spectrometry method with in-source fragmentation for rapid quantification of raspberry ketone.
J Food Drug Anal. 2019 Jul;27(3):778-785
Authors: Yuan B, Zhao D, Du R, Kshatriya D, Bello NT, Simon JE, Wu Q
Abstract
Raspberry ketone (RK) is the characteristic aromatic compound in raspberry (Rubus idaeus L.) with wide applications as food additive and anti-obesity agent. However, quantification of RK has presented difficulties in MS detection and reliable LC-MS method for RK analysis in literature is in limit to date. In order to facilitate quality control of raspberry derived products and RK metabolomics study, this study aimed to develop a validated and sensitive UHPLC-MS/MS method. Strong in-source fragmentation was noted and the fragmental ion of 107 m/z produced was selected as the precursor ion for MRM detection, and as such the electrospray ionization performance was optimized by fractional factorial design to accommodate such ion-source dissociation behavior as well as its moderate volatility. A pathway involving the formation of quinone-like structure with strong conjugation was proposed to explain the intense in-source fragmentation. The MRM transition was optimized with product ion of 77 m/z selected as the quantifier ion. The method featured low limit of quantification of ∼2 ng/mL and allowed for rapid detection of RK in fresh raspberries following direct sample preparation. RK contents were found to be higher from locally grown and harvested farm sources compared to commercial products shipped into the state, and higher in those at late-stage compared with early-stage maturity. No correlations in RK content between organic and non-organic labels were noted.
PMID: 31324293 [PubMed - in process]

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Human Breast Milk Promotes the Secretion of Potentially Beneficial Metabolites by Probiotic Lactobacillus reuteri DSM 17938.
Nutrients. 2019 Jul 09;11(7):
Authors: Mai TT, Tran DQ, Roos S, Rhoads JM, Liu Y
Abstract
Human breast milk (HBM) may have beneficial effects on Lactobacillus reuteri DSM 17938 (LR 17938) -mediated immunomodulation. We aimed to determine the effects of HBM on proliferation of LR 17938 in vitro and its associated proteins and metabolites in culture, in order to provide mechanistic insights into the health benefits of LR 17938. LR 17938 was cultured anaerobically in MRS bacterial culture media, HBM (from 6 mothers), and 2 types of cow-milk formula. The colony-forming unit (CFU) was calculated to evaluate LR 17938 growth. Sixteen-hour-fermented supernatants were used for metabolomics, and bacterial lysates were used for proteomics analysis. We found that growth of LR 17938 was 10 times better in HBM than in formula. We detected 261/452 metabolites upregulated when LR 17938 cultured in HBM compared to in formula, mainly participating in the glyoxylate cycle (succinate), urea cycle (citrulline), methionine methylation (N-acetylcysteine), and polyamine synthesis (spermidine). The significantly up-regulated enzymes were also involved in the formation of acetyl-CoA in the glyoxylate cycle and the antioxidant N-acetylcysteine. In conclusion, HBM enhances the growth of LR 17938 compared to formula and promotes LR 17938-associated metabolites that relate to energy and antioxidant status, which may be linked to the physiological effects of L. reuteri.
PMID: 31323989 [PubMed - in process]

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Metabolomic Studies of Tissue Injury in Nonhuman Primates Exposed to Gamma-Radiation.
Int J Mol Sci. 2019 Jul 09;20(13):
Authors: Cheema AK, Mehta KY, Rajagopal MU, Wise SY, Fatanmi OO, Singh VK
Abstract
Exposure to ionizing radiation induces a complex cascade of systemic and tissue-specific responses that lead to functional impairment over time in the surviving population. However, due to the lack of predictive biomarkers of tissue injury, current methods for the management of survivors of radiation exposure episodes involve monitoring of individuals over time for the development of adverse clinical symptoms and death. Herein, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that were exposed to a single dose of 7.2 Gy whole-body 60Co γ-radiation that either survived or succumbed to radiation toxicities over a 60-day period. This study involved the delineation of the radiation effects in the liver, kidney, jejunum, heart, lung, and spleen. We found robust metabolic changes in the kidney and liver and modest changes in other tissue types at the 60-day time point in a cohort of NHPs. Remarkably, we found significant elevation of long-chain acylcarnitines in animals that were exposed to radiation across multiple tissue types underscoring the role of this class of metabolites as a generic indicator of radiation-induced normal tissue injury. These studies underscore the utility of a metabolomics approach for delineating anticipatory biomarkers of exposure to ionizing radiation.
PMID: 31323921 [PubMed - in process]

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1H HR-MAS NMR-Based Metabolomics of Cancer Cells in Response to Treatment with the Diruthenium Trithiolato Complex [(p-MeC6H4iPr)2Ru2(SC6H4-p-But)3]+ (DiRu-1).
Metabolites. 2019 Jul 18;9(7):
Authors: Primasová H, Paul LEH, Diserens G, Primasová E, Vermathen P, Vermathen M, Furrer J
Abstract
The trithiolato bridged diruthenium complex DiRu-1 [(p-MeC6H4iPr)2Ru2(SC6H4-p-But)3]+ is highly cytotoxic against various cancer cell lines, but its exact mode of action remains unknown. The present 1H HR-MAS NMR-based metabolomic study was performed on ovarian cancer cell line A2780, on its cis-Pt resistant variant A2780cisR, and on the cell line HEK-293 treated with 0.03 µM and 0.015 µM of DiRu-1 corresponding to full and half IC50 doses, respectively, to investigate the mode of action of this ruthenium complex. The resulting changes in the metabolic profile of the cell lines were studied using HR-MAS NMR of cell lysates and a subsequent statistical analysis. We show that DiRu-1 in a 0.03 µM dose has significant impact on the levels of a number of metabolites, such as glutamine, glutamate, glutathione, cysteine, lipid, creatine, lactate, and acetate, especially pronounced in the A2780cisR cell line. The IC50/2 dose shows some significant changes, but full IC50 appears to be necessary to observe the full effect. Overall, the metabolic changes observed suggest that redox homeostasis, the Warburg effect, and the lipid metabolism are affected by DiRu-1.
PMID: 31323867 [PubMed]

28 new pubmed citations were retrieved for your search.
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metabolomics
These pubmed results were generated on 2019/07/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2019/07/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.

20 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2019/07/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.

20 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2019/07/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.

Shift in the paradigm towards next-generation microbiology.
FEMS Microbiol Lett. 2019 Jul 17;:
Authors: Stres B, Kronegger L
Abstract
In this work, the position of contemporary microbiology is considered from the perspective of scientific success, and a list of historical points and lessons learned from the fields of medical microbiology, microbial ecology and systems biology are presented. In addition, patterns in the development of top-down research topics that emerged over time as well as overlapping ideas and personnel, which are the first signs of trans-domain research activities in the fields of metagenomics, metaproteomics, metatranscriptomics and metabolomics, are explored through analysis of the publication networks of 28.654 papers using the computer programme Pajek. The current state of affairs is defined, and the need for meta-analyses to leverage publication biases in the field of microbiology is put forward as a very important emerging field of microbiology, especially since microbiology is progressively dealing with multiscale systems. Consequently, the need for cross-fertilisation with other fields/disciplines instead of 'more microbiology' is needed to advance the field of microbiology as such. The reader is directed to consider how novel technologies, the introduction of big data approaches and artificial intelligence have transformed microbiology into a multi-scale field and initiated a shift away from its history of mostly manual work and towards a largely technology-, data- and statistics-driven discipline that is often coupled with automation and modelling.
PMID: 31314103 [PubMed - as supplied by publisher]

Systemic and local metabolic alterations in sleep deprivation-induced stress: A multi-platform mass- spectrometry-based lipidomics and metabolomics approach.
J Proteome Res. 2019 Jul 17;:
Authors: Yoon SJ, Long NP, Jung KH, Kim HM, Hong YJ, Fang Z, Kim SJ, Kim TJ, Anh NH, Hong SS, Kwon SW
Abstract
Sleep deprivation (SD) is known to be associated with metabolic disorders and chronic diseases. Complex metabolic alterations induced by SD at the omics scale and the associated biomarker candidates have been proposed. However, in vivo systemic and local metabolic shift patterns of the metabolome and lipidome in acute and chronic partial SD models remain to be elucidated. In the present study, the serum, hypothalamus, and hippocampus CA1 of sleep-deprived rats (SD rats) from acute and chronic sleep restriction models were analyzed using three different omics platforms for the discovery and mechanistic assessment of systemic and local SD-induced dysregulated metabolites. We found a similar pattern of systemic metabolome alterations between two models, for which the area under the curve (AUC) of receiver operating characteristic (ROC) curves was AUC = 0.813 and 0.836 with the pseudotargeted and untargeted metabolomics approach, respectively. However, SD-induced systemic lipidome alterations were significantly different and appeared to be model-dependent (AUC = 0.374). Comprehensive pathway analysis of the altered lipidome and metabolome in the hypothalamus indicated the abnormal behavior of eight metabolic and lipid metabolic pathways. The metabolism of the hippocampus CA1 was subtle in two SD models. Collectively, these results extend our understanding of the quality of sleep and suggest metabolic targets in developing diagnostic biomarkers for better SD control.
PMID: 31313932 [PubMed - as supplied by publisher]

Nutrition and Metabolic Profiles in the Natural History of Dementia: Recent Insights from Systems Biology and Life Course Epidemiology.
Curr Nutr Rep. 2019 Jul 16;:
Authors: Lefèvre-Arbogast S, Wagner M, Proust-Lima C, Samieri C
Abstract
PURPOSE OF REVIEW: Worldwide, approximately 50 million people have dementia (mostly Alzheimer's disease). Dementia results from a multicomponent pathophysiology that follows complex dynamics over many years before symptoms become apparent. Nutrition may represent a target of choice for the primary prevention of dementia; however, there is still no firm answer on how to prevent dementia efficiently. We provide a broad overview of recent studies leveraging system biology and life-long epidemiology to address the multidimensionality and dynamical patterns underlying dementia and improve knowledge on the link between nutrition, cardiometabolic health and dementia risk.
RECENT FINDINGS: The aging of reference population-based cohort studies, the increasing availability of cutting-edge biomarkers (e.g., brain imaging, metabolomics) and the refinement of statistical tools to model complex exposures and dynamical health outcomes have yielded substantial progress in the understanding of dementia. Systems biology coupled with life-course epidemiology will pave the way toward novel precision nutrition approaches for prevention and management of dementia.
PMID: 31313074 [PubMed - as supplied by publisher]

Modified HEPES one-pot synthetic strategy for gold nanostars.
R Soc Open Sci. 2019 Jun;6(6):190160
Authors: Mulder DW, Phiri MM, Jordaan A, Vorster BC
Abstract
Gold nanostars are being used more regularly in the biosensing field. Despite their useful attributes, there is still a need to optimize aspects of the synthesis and stability. The seedless, synthetic method comprising 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) is a facile, rapid method; however, it produces heteromorphic nanostars. The modification of a HEPES method resulted in a silver-assisted, seedless gold nanostar synthesis method. The nanostars resulting from this method were monodispersed, multi-branched and approximately 37 ± 2 nm in diameter. It proved to be a repeatable method that produced homogeneous and robust nanostars. Once functionalized with polyvinylpyrrolidone 10 000, the new nanostars were observed to be stable in various environments such as salt, ionic strength and cell culture medium. In conclusion, the addition of the silver nitrate improved the morphology of the reported HEPES nanostars for the purpose of nanobiosensor development.
PMID: 31312487 [PubMed]

Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation.
Mol Genet Metab. 2019 Jul 09;:
Authors: Haijes HA, de Sain-van der Velden MGM, Prinsen HCMT, Willems AP, van der Ham M, Gerrits J, Couse MH, Friedman JM, van Karnebeek CDM, Selby KA, van Hasselt PM, Verhoeven-Duif NM, Jans JJM
Abstract
BACKGROUND: NGLY1-CDDG is a congenital disorder of deglycosylation caused by a defective peptide:N-glycanase (PNG). To date, all but one of the reported patients have been diagnosed through whole-exome or whole-genome sequencing, as no biochemical marker was available to identify this disease in patients. Recently, a potential urinary biomarker was reported, but the data presented suggest that this marker may be excreted intermittently.
METHODS: In this study, we performed untargeted direct-infusion high-resolution mass spectrometry metabolomics in seven dried blood spots (DBS) from four recently diagnosed NGLY1-CDDG patients, to test for small-molecule biomarkers, in order to identify a potential diagnostic marker. Results were compared to 125 DBS of healthy controls and to 238 DBS of patients with other diseases.
RESULTS: We identified aspartylglycosamine as the only significantly increased compound with a median Z-score of 4.8 (range: 3.8-8.5) in DBS of NGLY1-CDDG patients, compared to a median Z-score of -0.1 (range: -2.1-4.0) in DBS of healthy controls and patients with other diseases.
DISCUSSION: The increase of aspartylglycosamine can be explained by lack of function of PNG. PNG catalyzes the cleavage of the proximal N-acetylglucosamine residue of an N-glycan from the asparagine residue of a protein, a step in the degradation of misfolded glycoproteins. PNG deficiency results in a single N-acetylglucosamine residue left attached to the asparagine residue which results in free aspartylglycosamine when the glycoprotein is degraded. Thus, we here identified aspartylglycosamine as the first potential small-molecule biomarker in DBS for NGLY1-CDDG, making a biochemical diagnosis for NGLY1-CDDG potentially feasible.
PMID: 31311714 [PubMed - as supplied by publisher]